Stereoretentive Norrish-Yang Photocyclization Mediated by Hydrogen Bonding.

The Norrish-Yang photocyclization of aryl alkyl ketones is a classical photochemical transformation that proceeds through triplet 1,4-diradicals whose conformations govern the fate of the reaction. Directing the reactivity of these diradicals is difficult because they can evolve through competing pathways, including cyclization and Norrish type II fragmentation. Achieving stereocontrol is even more challenging because radicals generated from enantiopure substrates are expected to undergo rapid configurational scrambling. Here we report a stereoretentive Norrish-Yang photocyclization of enantiopure aryl alkyl ketones enabled by hydrogen-bond-guided conformational control of the photogenerated 1,4-diradical. Hydrogen-bonding units encoded within the chiral substrate bias the reactive diradical manifold toward cyclization while suppressing fragmentation and stereochemical erosion. The reaction affords highly enantioenriched spirocyclobutanol-containing amines and related cyclobutanols bearing two stereocenters, with high enantiospecificity across a range of amino-acid-derived substrates.